Insulin Resistant Metastatic Breast Cancer Patients Fare Worse

Metastatic breast cancer patients with insulin resistance have a significantly worse prognosis, according to the results of a study (abstract #514) presented at the 2014 American Society of Clinical Oncology (ASCO) Annual Meeting, held May 30–June 3, in Chicago.

Even after adjusting for other prognostic factors such as age, endocrine status of tumor, visceral disease, and body mass index (BMI), advanced breast cancer patients with insulin resistance had a statistically significant higher risk of disease progression (P = .035).

Alessandra Gennari, MD, PhD, of the National Cancer Research Institute in Genoa, Italy, and colleagues assessed the impact of insulin resistance on prognosis in 87 women with metastatic breast cancer who were taking part in a first-line clinical trial of non-pegylated liposomal doxorubicin plus cyclophosphamide. Insulin resistance was measured using the homeostasis model assessment (HOMA), a way to estimate beta cell function and insulin sensitivity based on a reference, non-diabetic population. Insulin resistance was defined as a HOMA index of greater than 2.5.

While the overall median progression-free survival (PFS) in the trial was 9 months, the median PFS was 8 months in women with insulin resistance compared with 14 months for those who did not have insulin resistance (P = .04).

­“We found that insulin resistant patients had a significantly worse prognosis,” said Gennari. “This means that there is a clear need to find alternative treatment strategies for this patient subset.”

Women in the study were followed up for a median of 15 months. In the study, 48.4% of the women were insulin resistant, 41% were overweight with a BMI between 25 and 30, and 19.2% of the women were obese (BMI greater than 30). The median age of the women was 61, and ages ranged from 36 to 77 years.

Eighty-seven percent of the women had hormone-receptor–positive disease and 63.6% of the women had visceral metastases.

John P. Pierce, PhD, professor of family and preventive medicine at the University of California San Diego Moores Cancer Center, previously linked chronic hyperglycemia in early breast cancer patients to a worse overall long-term survival. “In our study and others, there is consistency in the conclusion that diabetes is a comorbidity that significantly increases the risk of an early mortality,” Pierce told Cancer Network.

Women with breast cancer who have type 2 diabetes or glucose intolerance has been linked to a poorer overall survival. Still, the association between insulin levels, diabetes, and metastatic breast cancer is not clear.

“Insulin resistance is associated with a pro-inflammatory state that may be responsible for treatment failure,” said Gennari. “We must also consider that tissue insulin sensitivity may be different from overall insulin sensitivity, which is assessed by the HOMA index, and that breast cancer tissues may also have different insulin sensitivity.”

Gennari and colleagues are currently analyzing breast cancer tissue for insulin resistance using preclinical animal models to help tease out whether breast tissue has different responses to insulin compared to other tissue types.